Abstract

Microscopic imaging of cellular motility has recently advanced from two dimensions to three dimensions for applications in drug development. However, significant degradation in resolution occurs with increasing imaging depth, limiting access to motility information from deep inside the sample. Here, digital holographic optical coherence imaging is adapted to allow visualization of motility in tissue at depths inaccessible to conventional motility assay approaches. This method tracks the effect of cytoskeletal anti-cancer drugs on tissue inside its natural three-dimensional environment using time-course measurement of motility within tumor tissue.

© 2007 Optical Society of America

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  1. R. D. Vale, "The molecular motor toolbox for intracellular transport," Cell 112, 467-480 (2003),.
    [CrossRef] [PubMed]
  2. R. D. Vale and R. A. Milligan, "The way things move: Looking under the hood of molecular motor proteins," Science 288, 88-95 (2000).
    [CrossRef]
  3. E. Karsenti and I. Vernos, "The mitotic spindle: A self-made machine," Science 294, 543-547 (2001).
    [CrossRef] [PubMed]
  4. N. Hirokawa, "Kinesin and dynein superfamily proteins and the mechanism of organelle transport," Science 279, 519-526 (1998).
    [CrossRef] [PubMed]
  5. A. Desai and T. J. Mitchison, "Microtubule polymerization dynamics," Annu. Rev. Cell Dev. Biol. 13. 83-117 (1997).
    [CrossRef] [PubMed]
  6. J. R. Peterson and T. J. Mitchison, "Small molecules, big impact: A history of chemical inhibitors and the cytoskeleton," Chem. Biol. 9, 1275-1285 (2002).
    [CrossRef] [PubMed]
  7. M. A. Jordan and L. Wilson, "Microtubules and actin filaments: dynamic targets for cancer chemotherapy," Curr. Opin. Cell Biol. 10, 123-130 (1998).
    [CrossRef] [PubMed]
  8. T. D. Pollard and G. G. Borisy, "Cellular motility driven by assembly and disassembly of actin filaments," Cell 112, 453-465 (2003).
    [CrossRef] [PubMed]
  9. E. Cukierman, R. Pankov, D. R. Stevens, and K. M. Yamada, "Taking cell-matrix adhesions to the third dimension," Science 294, 1708-1712 (2001).
    [CrossRef] [PubMed]
  10. D. J. Webb and A. F. Horwitz, "New dimensions in cell migration," Nat. Cell Biol. 5, 690-692 (2003).
    [CrossRef] [PubMed]
  11. W. E. Moerner and D. P. Fromm, "Methods of single-molecule fluorescence spectroscopy and microscopy," Rev. Sci. Instrum. 74, 3597-3619 (2003).
    [CrossRef]
  12. R. H. Webb, "Confocal optical microscopy," Rep. Prog. Phys. 59, 427-471 (1996).
    [CrossRef]
  13. M. D. Cahalan, I. Parker, S. H. Wei, and M. J. Miller, "Two-photon tissue imaging: Seeing the immune system in a fresh light," Nat. Rev. Immunol. 2, 872-880 (2002).
    [CrossRef] [PubMed]
  14. K. Konig, "Multiphoton microscopy in life sciences," J. Microsc. 200, 83-104 (2000).
    [CrossRef] [PubMed]
  15. J. Sharpe, U. Ahlgren, P. Perry, B. Hill, A. Ross, J. Hecksher-Sorensen, R. Baldock, and D. Davidson, "Optical projection tomography as a tool for 3D microscopy and gene expression studies," Science 296, 541-545 (2002).
    [CrossRef] [PubMed]
  16. J. Huisken, J. Swoger, F. Del Bene, J. Wittbrodt, and E. H. Stelzer, "Optical sectioning deep inside live embryos by selective plane illumination microscopy," Science 305, 1007-1009 (2004).
    [CrossRef] [PubMed]
  17. M. G. L. Gustafsson, "Nonlinear structured-illumination microscopy: Wide-field fluorescence imaging with theoretically unlimited resolution," Proc. Natl. Acad. Sci. USA 102, 13081-13086 (2005).
    [CrossRef] [PubMed]
  18. T. A. Klar, S. Jakobs, M. Dyba, A. Egner, and S. W. Hell, "Fluorescence microscopy with diffraction resolution barrier broken by stimulated emission," Proc. Natl. Acad. Sci. USA 97, 8206-8210 (2000).
    [CrossRef] [PubMed]
  19. T. -C. Poon, T. Yatagai, and W. Jüptner, "Digital holography - coherent optics of the 21st century: introduction," Appl. Opt. 45, 821-821 (2006).
    [CrossRef]
  20. U. Schnars and W. P. O Jüptner, "Direct recording and numerical reconstruction of holograms," Meas. Sci. Technol. 13, R85-R101 (2002).
    [CrossRef]
  21. P. Massatsch, F. Charrière, E. Cuche, P. Marquet, and C. D. Depeursinge, "Time-domain optical coherence tomography with digital holographic microscopy," Appl. Opt. 44, 1806-1812 (2005).
    [CrossRef] [PubMed]
  22. K. Jeong, J. J. Turek, and D. D. Nolte, "Fourier-domain digital holographic optical coherence imaging of living tissue," Appl. Opt. 46, 4999-5008 (2007)
    [CrossRef] [PubMed]
  23. J. G. Fujimoto, "Optical coherence tomography for ultrahigh resolution in vivo imaging," Nat. Biotechnol. 21, 1361-1367 (2003).
    [CrossRef] [PubMed]
  24. A. F. Fercher, W. Drexler, C. K. Hitzenberger, and T. Lasser, "Optical coherence tomography - principles and applications," Rep. Prog. Phys. 66, 239-303 (2003).
    [CrossRef]
  25. P. Yu, M. Mustata, L. Peng, J. J. Turek, M. R. Melloch, P. M. French, and D. D. Nolte, "Holographic optical coherence imaging of rat osteogenic sarcoma tumor spheroids," Appl. Opt. 43, 4862-4873 (2004).
    [CrossRef] [PubMed]

2007 (1)

2006 (1)

2005 (2)

P. Massatsch, F. Charrière, E. Cuche, P. Marquet, and C. D. Depeursinge, "Time-domain optical coherence tomography with digital holographic microscopy," Appl. Opt. 44, 1806-1812 (2005).
[CrossRef] [PubMed]

M. G. L. Gustafsson, "Nonlinear structured-illumination microscopy: Wide-field fluorescence imaging with theoretically unlimited resolution," Proc. Natl. Acad. Sci. USA 102, 13081-13086 (2005).
[CrossRef] [PubMed]

2004 (2)

J. Huisken, J. Swoger, F. Del Bene, J. Wittbrodt, and E. H. Stelzer, "Optical sectioning deep inside live embryos by selective plane illumination microscopy," Science 305, 1007-1009 (2004).
[CrossRef] [PubMed]

P. Yu, M. Mustata, L. Peng, J. J. Turek, M. R. Melloch, P. M. French, and D. D. Nolte, "Holographic optical coherence imaging of rat osteogenic sarcoma tumor spheroids," Appl. Opt. 43, 4862-4873 (2004).
[CrossRef] [PubMed]

2003 (6)

J. G. Fujimoto, "Optical coherence tomography for ultrahigh resolution in vivo imaging," Nat. Biotechnol. 21, 1361-1367 (2003).
[CrossRef] [PubMed]

A. F. Fercher, W. Drexler, C. K. Hitzenberger, and T. Lasser, "Optical coherence tomography - principles and applications," Rep. Prog. Phys. 66, 239-303 (2003).
[CrossRef]

D. J. Webb and A. F. Horwitz, "New dimensions in cell migration," Nat. Cell Biol. 5, 690-692 (2003).
[CrossRef] [PubMed]

W. E. Moerner and D. P. Fromm, "Methods of single-molecule fluorescence spectroscopy and microscopy," Rev. Sci. Instrum. 74, 3597-3619 (2003).
[CrossRef]

R. D. Vale, "The molecular motor toolbox for intracellular transport," Cell 112, 467-480 (2003),.
[CrossRef] [PubMed]

T. D. Pollard and G. G. Borisy, "Cellular motility driven by assembly and disassembly of actin filaments," Cell 112, 453-465 (2003).
[CrossRef] [PubMed]

2002 (4)

J. R. Peterson and T. J. Mitchison, "Small molecules, big impact: A history of chemical inhibitors and the cytoskeleton," Chem. Biol. 9, 1275-1285 (2002).
[CrossRef] [PubMed]

M. D. Cahalan, I. Parker, S. H. Wei, and M. J. Miller, "Two-photon tissue imaging: Seeing the immune system in a fresh light," Nat. Rev. Immunol. 2, 872-880 (2002).
[CrossRef] [PubMed]

J. Sharpe, U. Ahlgren, P. Perry, B. Hill, A. Ross, J. Hecksher-Sorensen, R. Baldock, and D. Davidson, "Optical projection tomography as a tool for 3D microscopy and gene expression studies," Science 296, 541-545 (2002).
[CrossRef] [PubMed]

U. Schnars and W. P. O Jüptner, "Direct recording and numerical reconstruction of holograms," Meas. Sci. Technol. 13, R85-R101 (2002).
[CrossRef]

2001 (2)

E. Cukierman, R. Pankov, D. R. Stevens, and K. M. Yamada, "Taking cell-matrix adhesions to the third dimension," Science 294, 1708-1712 (2001).
[CrossRef] [PubMed]

E. Karsenti and I. Vernos, "The mitotic spindle: A self-made machine," Science 294, 543-547 (2001).
[CrossRef] [PubMed]

2000 (3)

R. D. Vale and R. A. Milligan, "The way things move: Looking under the hood of molecular motor proteins," Science 288, 88-95 (2000).
[CrossRef]

T. A. Klar, S. Jakobs, M. Dyba, A. Egner, and S. W. Hell, "Fluorescence microscopy with diffraction resolution barrier broken by stimulated emission," Proc. Natl. Acad. Sci. USA 97, 8206-8210 (2000).
[CrossRef] [PubMed]

K. Konig, "Multiphoton microscopy in life sciences," J. Microsc. 200, 83-104 (2000).
[CrossRef] [PubMed]

1998 (2)

N. Hirokawa, "Kinesin and dynein superfamily proteins and the mechanism of organelle transport," Science 279, 519-526 (1998).
[CrossRef] [PubMed]

M. A. Jordan and L. Wilson, "Microtubules and actin filaments: dynamic targets for cancer chemotherapy," Curr. Opin. Cell Biol. 10, 123-130 (1998).
[CrossRef] [PubMed]

1997 (1)

A. Desai and T. J. Mitchison, "Microtubule polymerization dynamics," Annu. Rev. Cell Dev. Biol. 13. 83-117 (1997).
[CrossRef] [PubMed]

1996 (1)

R. H. Webb, "Confocal optical microscopy," Rep. Prog. Phys. 59, 427-471 (1996).
[CrossRef]

Ahlgren, U.

J. Sharpe, U. Ahlgren, P. Perry, B. Hill, A. Ross, J. Hecksher-Sorensen, R. Baldock, and D. Davidson, "Optical projection tomography as a tool for 3D microscopy and gene expression studies," Science 296, 541-545 (2002).
[CrossRef] [PubMed]

Baldock, R.

J. Sharpe, U. Ahlgren, P. Perry, B. Hill, A. Ross, J. Hecksher-Sorensen, R. Baldock, and D. Davidson, "Optical projection tomography as a tool for 3D microscopy and gene expression studies," Science 296, 541-545 (2002).
[CrossRef] [PubMed]

Borisy, G. G.

T. D. Pollard and G. G. Borisy, "Cellular motility driven by assembly and disassembly of actin filaments," Cell 112, 453-465 (2003).
[CrossRef] [PubMed]

Cahalan, M. D.

M. D. Cahalan, I. Parker, S. H. Wei, and M. J. Miller, "Two-photon tissue imaging: Seeing the immune system in a fresh light," Nat. Rev. Immunol. 2, 872-880 (2002).
[CrossRef] [PubMed]

Charrière, F.

Cuche, E.

Cukierman, E.

E. Cukierman, R. Pankov, D. R. Stevens, and K. M. Yamada, "Taking cell-matrix adhesions to the third dimension," Science 294, 1708-1712 (2001).
[CrossRef] [PubMed]

Davidson, D.

J. Sharpe, U. Ahlgren, P. Perry, B. Hill, A. Ross, J. Hecksher-Sorensen, R. Baldock, and D. Davidson, "Optical projection tomography as a tool for 3D microscopy and gene expression studies," Science 296, 541-545 (2002).
[CrossRef] [PubMed]

Del Bene, F.

J. Huisken, J. Swoger, F. Del Bene, J. Wittbrodt, and E. H. Stelzer, "Optical sectioning deep inside live embryos by selective plane illumination microscopy," Science 305, 1007-1009 (2004).
[CrossRef] [PubMed]

Depeursinge, C. D.

Desai, A.

A. Desai and T. J. Mitchison, "Microtubule polymerization dynamics," Annu. Rev. Cell Dev. Biol. 13. 83-117 (1997).
[CrossRef] [PubMed]

Drexler, W.

A. F. Fercher, W. Drexler, C. K. Hitzenberger, and T. Lasser, "Optical coherence tomography - principles and applications," Rep. Prog. Phys. 66, 239-303 (2003).
[CrossRef]

Dyba, M.

T. A. Klar, S. Jakobs, M. Dyba, A. Egner, and S. W. Hell, "Fluorescence microscopy with diffraction resolution barrier broken by stimulated emission," Proc. Natl. Acad. Sci. USA 97, 8206-8210 (2000).
[CrossRef] [PubMed]

Egner, A.

T. A. Klar, S. Jakobs, M. Dyba, A. Egner, and S. W. Hell, "Fluorescence microscopy with diffraction resolution barrier broken by stimulated emission," Proc. Natl. Acad. Sci. USA 97, 8206-8210 (2000).
[CrossRef] [PubMed]

Fercher, A. F.

A. F. Fercher, W. Drexler, C. K. Hitzenberger, and T. Lasser, "Optical coherence tomography - principles and applications," Rep. Prog. Phys. 66, 239-303 (2003).
[CrossRef]

French, P. M.

Fromm, D. P.

W. E. Moerner and D. P. Fromm, "Methods of single-molecule fluorescence spectroscopy and microscopy," Rev. Sci. Instrum. 74, 3597-3619 (2003).
[CrossRef]

Fujimoto, J. G.

J. G. Fujimoto, "Optical coherence tomography for ultrahigh resolution in vivo imaging," Nat. Biotechnol. 21, 1361-1367 (2003).
[CrossRef] [PubMed]

Gustafsson, M. G. L.

M. G. L. Gustafsson, "Nonlinear structured-illumination microscopy: Wide-field fluorescence imaging with theoretically unlimited resolution," Proc. Natl. Acad. Sci. USA 102, 13081-13086 (2005).
[CrossRef] [PubMed]

Hecksher-Sorensen, J.

J. Sharpe, U. Ahlgren, P. Perry, B. Hill, A. Ross, J. Hecksher-Sorensen, R. Baldock, and D. Davidson, "Optical projection tomography as a tool for 3D microscopy and gene expression studies," Science 296, 541-545 (2002).
[CrossRef] [PubMed]

Hell, S. W.

T. A. Klar, S. Jakobs, M. Dyba, A. Egner, and S. W. Hell, "Fluorescence microscopy with diffraction resolution barrier broken by stimulated emission," Proc. Natl. Acad. Sci. USA 97, 8206-8210 (2000).
[CrossRef] [PubMed]

Hill, B.

J. Sharpe, U. Ahlgren, P. Perry, B. Hill, A. Ross, J. Hecksher-Sorensen, R. Baldock, and D. Davidson, "Optical projection tomography as a tool for 3D microscopy and gene expression studies," Science 296, 541-545 (2002).
[CrossRef] [PubMed]

Hirokawa, N.

N. Hirokawa, "Kinesin and dynein superfamily proteins and the mechanism of organelle transport," Science 279, 519-526 (1998).
[CrossRef] [PubMed]

Hitzenberger, C. K.

A. F. Fercher, W. Drexler, C. K. Hitzenberger, and T. Lasser, "Optical coherence tomography - principles and applications," Rep. Prog. Phys. 66, 239-303 (2003).
[CrossRef]

Horwitz, A. F.

D. J. Webb and A. F. Horwitz, "New dimensions in cell migration," Nat. Cell Biol. 5, 690-692 (2003).
[CrossRef] [PubMed]

Huisken, J.

J. Huisken, J. Swoger, F. Del Bene, J. Wittbrodt, and E. H. Stelzer, "Optical sectioning deep inside live embryos by selective plane illumination microscopy," Science 305, 1007-1009 (2004).
[CrossRef] [PubMed]

Jakobs, S.

T. A. Klar, S. Jakobs, M. Dyba, A. Egner, and S. W. Hell, "Fluorescence microscopy with diffraction resolution barrier broken by stimulated emission," Proc. Natl. Acad. Sci. USA 97, 8206-8210 (2000).
[CrossRef] [PubMed]

Jeong, K.

Jordan, M. A.

M. A. Jordan and L. Wilson, "Microtubules and actin filaments: dynamic targets for cancer chemotherapy," Curr. Opin. Cell Biol. 10, 123-130 (1998).
[CrossRef] [PubMed]

Jüptner, W.

Jüptner, W. P. O

U. Schnars and W. P. O Jüptner, "Direct recording and numerical reconstruction of holograms," Meas. Sci. Technol. 13, R85-R101 (2002).
[CrossRef]

Karsenti, E.

E. Karsenti and I. Vernos, "The mitotic spindle: A self-made machine," Science 294, 543-547 (2001).
[CrossRef] [PubMed]

Klar, T. A.

T. A. Klar, S. Jakobs, M. Dyba, A. Egner, and S. W. Hell, "Fluorescence microscopy with diffraction resolution barrier broken by stimulated emission," Proc. Natl. Acad. Sci. USA 97, 8206-8210 (2000).
[CrossRef] [PubMed]

Konig, K.

K. Konig, "Multiphoton microscopy in life sciences," J. Microsc. 200, 83-104 (2000).
[CrossRef] [PubMed]

Lasser, T.

A. F. Fercher, W. Drexler, C. K. Hitzenberger, and T. Lasser, "Optical coherence tomography - principles and applications," Rep. Prog. Phys. 66, 239-303 (2003).
[CrossRef]

Marquet, P.

Massatsch, P.

Melloch, M. R.

Miller, M. J.

M. D. Cahalan, I. Parker, S. H. Wei, and M. J. Miller, "Two-photon tissue imaging: Seeing the immune system in a fresh light," Nat. Rev. Immunol. 2, 872-880 (2002).
[CrossRef] [PubMed]

Milligan, R. A.

R. D. Vale and R. A. Milligan, "The way things move: Looking under the hood of molecular motor proteins," Science 288, 88-95 (2000).
[CrossRef]

Mitchison, T. J.

J. R. Peterson and T. J. Mitchison, "Small molecules, big impact: A history of chemical inhibitors and the cytoskeleton," Chem. Biol. 9, 1275-1285 (2002).
[CrossRef] [PubMed]

A. Desai and T. J. Mitchison, "Microtubule polymerization dynamics," Annu. Rev. Cell Dev. Biol. 13. 83-117 (1997).
[CrossRef] [PubMed]

Moerner, W. E.

W. E. Moerner and D. P. Fromm, "Methods of single-molecule fluorescence spectroscopy and microscopy," Rev. Sci. Instrum. 74, 3597-3619 (2003).
[CrossRef]

Mustata, M.

Nolte, D. D.

Pankov, R.

E. Cukierman, R. Pankov, D. R. Stevens, and K. M. Yamada, "Taking cell-matrix adhesions to the third dimension," Science 294, 1708-1712 (2001).
[CrossRef] [PubMed]

Parker, I.

M. D. Cahalan, I. Parker, S. H. Wei, and M. J. Miller, "Two-photon tissue imaging: Seeing the immune system in a fresh light," Nat. Rev. Immunol. 2, 872-880 (2002).
[CrossRef] [PubMed]

Peng, L.

Perry, P.

J. Sharpe, U. Ahlgren, P. Perry, B. Hill, A. Ross, J. Hecksher-Sorensen, R. Baldock, and D. Davidson, "Optical projection tomography as a tool for 3D microscopy and gene expression studies," Science 296, 541-545 (2002).
[CrossRef] [PubMed]

Peterson, J. R.

J. R. Peterson and T. J. Mitchison, "Small molecules, big impact: A history of chemical inhibitors and the cytoskeleton," Chem. Biol. 9, 1275-1285 (2002).
[CrossRef] [PubMed]

Pollard, T. D.

T. D. Pollard and G. G. Borisy, "Cellular motility driven by assembly and disassembly of actin filaments," Cell 112, 453-465 (2003).
[CrossRef] [PubMed]

Poon, T. -C.

Ross, A.

J. Sharpe, U. Ahlgren, P. Perry, B. Hill, A. Ross, J. Hecksher-Sorensen, R. Baldock, and D. Davidson, "Optical projection tomography as a tool for 3D microscopy and gene expression studies," Science 296, 541-545 (2002).
[CrossRef] [PubMed]

Schnars, U.

U. Schnars and W. P. O Jüptner, "Direct recording and numerical reconstruction of holograms," Meas. Sci. Technol. 13, R85-R101 (2002).
[CrossRef]

Sharpe, J.

J. Sharpe, U. Ahlgren, P. Perry, B. Hill, A. Ross, J. Hecksher-Sorensen, R. Baldock, and D. Davidson, "Optical projection tomography as a tool for 3D microscopy and gene expression studies," Science 296, 541-545 (2002).
[CrossRef] [PubMed]

Stelzer, E. H.

J. Huisken, J. Swoger, F. Del Bene, J. Wittbrodt, and E. H. Stelzer, "Optical sectioning deep inside live embryos by selective plane illumination microscopy," Science 305, 1007-1009 (2004).
[CrossRef] [PubMed]

Stevens, D. R.

E. Cukierman, R. Pankov, D. R. Stevens, and K. M. Yamada, "Taking cell-matrix adhesions to the third dimension," Science 294, 1708-1712 (2001).
[CrossRef] [PubMed]

Swoger, J.

J. Huisken, J. Swoger, F. Del Bene, J. Wittbrodt, and E. H. Stelzer, "Optical sectioning deep inside live embryos by selective plane illumination microscopy," Science 305, 1007-1009 (2004).
[CrossRef] [PubMed]

Turek, J. J.

Vale, R. D.

R. D. Vale, "The molecular motor toolbox for intracellular transport," Cell 112, 467-480 (2003),.
[CrossRef] [PubMed]

R. D. Vale and R. A. Milligan, "The way things move: Looking under the hood of molecular motor proteins," Science 288, 88-95 (2000).
[CrossRef]

Vernos, I.

E. Karsenti and I. Vernos, "The mitotic spindle: A self-made machine," Science 294, 543-547 (2001).
[CrossRef] [PubMed]

Webb, D. J.

D. J. Webb and A. F. Horwitz, "New dimensions in cell migration," Nat. Cell Biol. 5, 690-692 (2003).
[CrossRef] [PubMed]

Webb, R. H.

R. H. Webb, "Confocal optical microscopy," Rep. Prog. Phys. 59, 427-471 (1996).
[CrossRef]

Wei, S. H.

M. D. Cahalan, I. Parker, S. H. Wei, and M. J. Miller, "Two-photon tissue imaging: Seeing the immune system in a fresh light," Nat. Rev. Immunol. 2, 872-880 (2002).
[CrossRef] [PubMed]

Wilson, L.

M. A. Jordan and L. Wilson, "Microtubules and actin filaments: dynamic targets for cancer chemotherapy," Curr. Opin. Cell Biol. 10, 123-130 (1998).
[CrossRef] [PubMed]

Wittbrodt, J.

J. Huisken, J. Swoger, F. Del Bene, J. Wittbrodt, and E. H. Stelzer, "Optical sectioning deep inside live embryos by selective plane illumination microscopy," Science 305, 1007-1009 (2004).
[CrossRef] [PubMed]

Yamada, K. M.

E. Cukierman, R. Pankov, D. R. Stevens, and K. M. Yamada, "Taking cell-matrix adhesions to the third dimension," Science 294, 1708-1712 (2001).
[CrossRef] [PubMed]

Yatagai, T.

Yu, P.

Annu. Rev. Cell Dev. Biol. (1)

A. Desai and T. J. Mitchison, "Microtubule polymerization dynamics," Annu. Rev. Cell Dev. Biol. 13. 83-117 (1997).
[CrossRef] [PubMed]

Appl. Opt. (4)

Cell (2)

T. D. Pollard and G. G. Borisy, "Cellular motility driven by assembly and disassembly of actin filaments," Cell 112, 453-465 (2003).
[CrossRef] [PubMed]

R. D. Vale, "The molecular motor toolbox for intracellular transport," Cell 112, 467-480 (2003),.
[CrossRef] [PubMed]

Chem. Biol. (1)

J. R. Peterson and T. J. Mitchison, "Small molecules, big impact: A history of chemical inhibitors and the cytoskeleton," Chem. Biol. 9, 1275-1285 (2002).
[CrossRef] [PubMed]

Curr. Opin. Cell Biol. (1)

M. A. Jordan and L. Wilson, "Microtubules and actin filaments: dynamic targets for cancer chemotherapy," Curr. Opin. Cell Biol. 10, 123-130 (1998).
[CrossRef] [PubMed]

J. Microsc. (1)

K. Konig, "Multiphoton microscopy in life sciences," J. Microsc. 200, 83-104 (2000).
[CrossRef] [PubMed]

Meas. Sci. Technol. (1)

U. Schnars and W. P. O Jüptner, "Direct recording and numerical reconstruction of holograms," Meas. Sci. Technol. 13, R85-R101 (2002).
[CrossRef]

Nat. Biotechnol. (1)

J. G. Fujimoto, "Optical coherence tomography for ultrahigh resolution in vivo imaging," Nat. Biotechnol. 21, 1361-1367 (2003).
[CrossRef] [PubMed]

Nat. Cell Biol. (1)

D. J. Webb and A. F. Horwitz, "New dimensions in cell migration," Nat. Cell Biol. 5, 690-692 (2003).
[CrossRef] [PubMed]

Nat. Rev. Immunol. (1)

M. D. Cahalan, I. Parker, S. H. Wei, and M. J. Miller, "Two-photon tissue imaging: Seeing the immune system in a fresh light," Nat. Rev. Immunol. 2, 872-880 (2002).
[CrossRef] [PubMed]

Proc. Natl. Acad. Sci. USA (2)

M. G. L. Gustafsson, "Nonlinear structured-illumination microscopy: Wide-field fluorescence imaging with theoretically unlimited resolution," Proc. Natl. Acad. Sci. USA 102, 13081-13086 (2005).
[CrossRef] [PubMed]

T. A. Klar, S. Jakobs, M. Dyba, A. Egner, and S. W. Hell, "Fluorescence microscopy with diffraction resolution barrier broken by stimulated emission," Proc. Natl. Acad. Sci. USA 97, 8206-8210 (2000).
[CrossRef] [PubMed]

Rep. Prog. Phys. (2)

R. H. Webb, "Confocal optical microscopy," Rep. Prog. Phys. 59, 427-471 (1996).
[CrossRef]

A. F. Fercher, W. Drexler, C. K. Hitzenberger, and T. Lasser, "Optical coherence tomography - principles and applications," Rep. Prog. Phys. 66, 239-303 (2003).
[CrossRef]

Rev. Sci. Instrum. (1)

W. E. Moerner and D. P. Fromm, "Methods of single-molecule fluorescence spectroscopy and microscopy," Rev. Sci. Instrum. 74, 3597-3619 (2003).
[CrossRef]

Science (6)

J. Sharpe, U. Ahlgren, P. Perry, B. Hill, A. Ross, J. Hecksher-Sorensen, R. Baldock, and D. Davidson, "Optical projection tomography as a tool for 3D microscopy and gene expression studies," Science 296, 541-545 (2002).
[CrossRef] [PubMed]

J. Huisken, J. Swoger, F. Del Bene, J. Wittbrodt, and E. H. Stelzer, "Optical sectioning deep inside live embryos by selective plane illumination microscopy," Science 305, 1007-1009 (2004).
[CrossRef] [PubMed]

E. Cukierman, R. Pankov, D. R. Stevens, and K. M. Yamada, "Taking cell-matrix adhesions to the third dimension," Science 294, 1708-1712 (2001).
[CrossRef] [PubMed]

R. D. Vale and R. A. Milligan, "The way things move: Looking under the hood of molecular motor proteins," Science 288, 88-95 (2000).
[CrossRef]

E. Karsenti and I. Vernos, "The mitotic spindle: A self-made machine," Science 294, 543-547 (2001).
[CrossRef] [PubMed]

N. Hirokawa, "Kinesin and dynein superfamily proteins and the mechanism of organelle transport," Science 279, 519-526 (1998).
[CrossRef] [PubMed]

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Figures (6)

Fig. 1.
Fig. 1.

(a) Schematic of the DHOCI system: M, Mirror; f, focal length. (b) Digital reconstruction of diffuse paper with letter ®. Selections of real images from digital reconstructions of (c) a positive UASF target, (d) inside onion at a depth of 100 μm, and (e) inside an 800-μm-diameter rat tumor spheroid at a depth of 400 μm, respectively. Bars, 200 μm.

Fig. 2.
Fig. 2.

Mid cross-section images from fixed-depth sections of a healthy tumor (left) and a cross-linked tumor (right). The data (acquired at a fixed depth of 340 μm from the top of a 680-μm-diameter tumor) are shown with a vertical axis of time. The healthy tumor shows significant fluctuations, while the cross-linked tumor is static. Bar, 100 μm.

Fig. 3.
Fig. 3.

An example of the motility imaging for a healthy tumor. Average intensity maps (first column), standard deviation maps (second column), and motility maps (third column) are shown for center illumination (first row) and edge illumination (second row) of the tumor. Motility images were produced under the same experimental conditions with a time interval of one minute, only by changing the position of the healthy tumor. The healthy tumorBar, 100 μm.

Fig. 4.
Fig. 4.

Motility maps generated at nine different depths for (a) a healthy tumor and (b) a crosslinked tumor with a 680 μm diameter. Time interval between holograms was 1 second.

Fig. 5.
Fig. 5.

Motility maps showing the response of an 820-μm-diameter tumor (at a fixed depth of 350 μm from the tumor top) to 10 μg/ml nocodazole as a function of time (from healthy to 120 minutes later). Motility in the viable shell decreases with time, showing how nocodazole suppresses the activity of viable tumor cells. Bar, 100 μm.

Fig. 6.
Fig. 6.

Time-course measurements of NSD density (in the viable area) as a function of dose for (a) nocodazole, (b) colchicine, and (c) paclitaxel, respectively, showing dramatic motility decrease with increasing time and dose. (d) Reaction velocity (NSD/min) dose-response curves of three anti-neoplastic drugs, which are obtained from the characteristic time and magnitude of the time-response curves of NSD density in (a), (b), and (c).

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